Eur Respir J
1992, 5 , 1021-1022
Upper lobe infiltrate with cough, fever, fatigue
A. Biglino, G. De Rosa, F. Lipani
Case history
A 41 yr old housewife, orig ina lly from Sicily,
presented in June 1990 with a fever of five months
duration, dry cough and fatigue. She denied present
or previous occupational risks as we.ll as travel outside
ftaly during the previous J 0 yrs.
The patient appeared in good condition; physical
examination was negative for superficial lymph -
adenopathy. hepatosplenomegaly and pulmonary
findings. A left upper lobe pulmonary opacity was
detected at another hospital on r outine chest
roentgenogram; a fi ne-needle aspiration-biopsy was not
diagnostic.
Laboratory tests were within nom1al range with the
exception of erythrocyte sedimentation rate (ESR) (43
mm·h· 1) and of a mild hypochromic microcytic anae-
mia (Hb= 95 g·/' 1; mean corpuscular volume
(MCV)=74 J.l.~; blood iron= 230 J.l.g·/·1). Anti-human
immunodeficiency virus- I (HIV-I) specific antibodies
were repeatedly negative by enzyme immune-
assays . Circulating CD4+ cells were normal in
number (1, li5·J.l.l· 1) and CD4/CD 8 ratio was 2.18.
Fig. I. - a) Chest roentgenogram of the patient before treatment.
b) Tomograph ic detai l o f ldt uppe r lobe so li tary nodule.
Before turning the page: - interpret the roentgenogram and smear; - propose further examinations; •
suggest diagnosis.
Corresponde nce: A. Biglino. lsti tuto di Malauie lnfeu ivc Corso
Svizzera 164, Torino, Italy.
CASE FOR DIAGNOSIS
A 5 IU purified protein derivative (PPD) skin test was
negative. Serological tests for Hi stoplasma- and
Aspergillus-specific antibodies (immunodiffusion) and
circulating antigens (counter-immune-electrophoresis),
as well as indirect immmunofluorescence for
Legioneffa pneumophila antibodies were negative.
Chest roentgenograms confirmed previous findings
(fig. 1 a and b).
Bronchoscopy performed through an Olympus BF 20
fibrescope showed a normal bronchial tree until
subsegmentary branchings of the left upper bronchus.
Brushing and lavage of the left upper bronchus with
180 ml of saline solution were performed. Gram and
Ziehl-Neelsen stains on the lavage pellet were nega-
tive. Cultures of recovered bronchoalveolar lavage
fluid (BALF) on both plated and liquid Sabouraud
medium, on malt-agar medium, International Union
Against Tuberculosis (Mycobacterium) (IUTM) me-
dium and other common culture media were negative.
Cytological smears obtained from BALF showed
normal columnar bronchial cells an-anged in the pali-
sade and numerous histiocytes filled with cytoplasmic
periodic-acid-Schiff (PAS)-positive bodies (fig. 2).
Fig. 2. - Small clusters of PAS-posi tive bodies with in histiocytes
(arrow ) and between columnar bro nchia l cells. Inset: highe r
magnifi cation of a histiocyte with cytoplasmic PAS-positive bod -
ies. PAS: periodic-acid-Sc hiff.
TURN PAGE FOR DIAGNOSIS
1022 A. BIGLINO, G. DE ROSA, F. LIPANI
Interpretation of roentgenogram: solitary upper left
lobe pulmonary mass, consistent with either an
inflammatory or a neoplastic process.
Interpretation of smear microscopy: PAS-positive
bodies within histocytic cytoplasm and among bron-
chial cells, consistent with Histoplasma capsu.latum .
Diagnosis: pulmonary histoplasmosis
Treatment was started with fluconazole, 400
mg·day·' intravenously, and was continued for 20 days;
dosage was then reduced to 200 mg·day·' orally and
continued for 2 months. Complete radiological re-
gression of the left apical opacity was observed after
the first month of treatment. By that time, the ESR
and haematological parameters were also normalized.
One year after ending treatment the patient was in
good condition and chest roentgenogram was normal
(fig. 3).
Fig. 3. - Chest roentge nogram 11 months after starting treat-
ment.
Discussion
Histoplasmosis is a rare disease in Italy, as well as
in the rest of Europe, where imported cases from high-
risk countries usually predominate [lj. The reported
case, clearly acquired in Sicily, suggests that this dis-
ease should be considered routinely in the differential
diagnosis of nodular pulmonary opacities, particularly
in patients coming from southern Europe.
A non-invasive diagnostic approach could be
difficult in these patients, as serological techniques
based on antibody detection are often unsatisfactory in
non-disseminated histoplasmosis because of lack of
sensitivity f2, 3]. Even the more sensitive methods
based on circulating antigen detection, although highly
d iagnostic in disseminated histoplasmosis [4], are
flawed by a false-negative rate as high as 63% in
localized pulmonary disease [5). Finally, invasive di-
agnostic procedures such as fine-needle aspiration/
biopsy could be unsuccesful in the case of small
multiple nodular lesions, and are associated with
pneumothorax in about 18% of cases [6].
Although reports evaluating fibreoptic bronchoscopy
in the diagnosis of this disease are very few , the di-
agnostic usefulness of bronchoscopy in pulmonary
histoplasmosis has already been stressed, although
some perplexities exist as far as solitary nodules are
concerned [5]. Our observation suggests that cyto-
logical examination of material recovered from BAL
may represent a reasonable and safe alternative to
fine-needle aspiration-biopsy and confirms its superi-
ority to serological techniques in the diagnosis of
solitary nodular manifestations of pulmonary histo-
plasmosis. Finally, the absence of positive fungal
cultures from recovered lavage fluid should not cause
the diagnosis of pulmonary histoplasmosis to be dis-
carded, as cultures can either take several weeks or
yield negative results [5, 7]. In our case, prompt im-
provement with fluconazole alone, with disappearance
of chest radiological abnormality strongly supports this
diagnosis.
References
1. Davies SF. - Histoplasmosis: update 1989. Semin
Respir Infect, 1990; 5: 93-104.
2. Davies SF. Diagnosis of pulmonary funga l
infections. Semin Respir lnfecl, 1988; 3: 162-171.
3. Wheat LJ. - Diagnosis and management of histo-
plasmosis. Eur J Clin Microbial lllfecl Dis, 1989; 8:
480-490.
4. Wheat LJ, Kohler RB, Tewari RP. - Diagnosis of
disseminated histoplasmosis by detection of Histoplasma
capsulatum antigen in serum and urine specimens. N Engl
J Med, 1986; 314: 83-88.
5. Prechter GC, Prakash UBS. - Bronchoscopy in the
diagnosis of pulmonary histoplasmosis. Chest, 1989; 5:
1033- 1036.
6. Conces DJ, Clark SA, Tarver RD, Schwenk GR. -
Transthoracic aspiration needle biopsy; value in the diag-
nosis of pulmonary infections. Am J Roentgenol, 1989;
152: 31-34.
7. Johnson PC, Sarosi GA . Community-acquired
fungal pneumonias. Semin Respir Infect, 1989; 4: 56-63.